3-hydroxy-2,2-dimethylpropyl 3-hydroxy-2,2-dimethylpropionate

Endpoint summary

Description of key information

oral: LD50 (rat) = 8000 mg/kg bw
inhalation risk test: no mortality

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is comparable to OECD Guideline 401 with acceptable restrictions (partly limited documentation, e.g. no details about the test substance; post exposure observation period 7 days)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Mean body weight at initiation: 180-208g (males), 144-170g (females)
No further details.

Route of administration:

oral: gavage

Vehicle:

other: aqueous suspension with 0.5% carboxymethylcellulose

Details on oral exposure:

concentration in test solution 35%; application volume 28.5 or 13.3 ml/kg bw, respectively; no data about fasting prior to application.

Doses:

4640 or 10000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations:daily
- weighing: day 0, 2, or 7
- Necropsy of survivors and rats found dead

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

8 000 mg/kg bw

Remarks on result:

other: for males and females combined

Mortality:

Data on mortality are presented in the Table below. At the high dose levels rats died within 4 h as well as one female at the low dose level. Females more susceptible than males.

Clinical signs:

other: Clinical signs in both dose groups: immediately after gavage prone and side position, apathy, atony, gasping, cyanosis; 2nd day red encrusted noses; symptoms still present after 2 days. No symptoms detected 5 days after application.

Gross pathology:

Surviving rats: darkened liver and some cases of splenomegaly.
Rats found dead: dilatation of the heart; hyperemia

Other findings:

no data

Mortality in male and female rats after gavage; observation period 7 days

Dose in mg/kg bw	Males	Females
4640	0/5	1/5
10000	3/5	4/5

Conclusions:

The oral LD50 is 8000 mg/kg bw in male and female rats combined.

Executive summary:

The study is comparable to OECD Guideline 401 with acceptable restrictions (partly limited documentation, e.g. no details about the test substance; post exposure observation period 7 days)

Groups of 5 male and 5 female rats were gavaged with 35% aqueous suspension at dose levels of 4640 and 10000 mg/kg bw. The post exposure observation period was 7 days. Clinical signs occurred immediately after gavage: prone and side position, apathy, atony, gasping, cyanosis, and 2nd day red encrusted noses; symptoms were still present after 2 days. No symptoms were detected 5 days after application.. Generally, females were more susceptible than males. The body weight gain was not reduced. Necropsy revealed dilatated heart and some cases of splenomegaly.

Conclusion: The oral LD50 is 8000 mg/kg bw in male and female rats combined.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

8 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The test demonstrates that there is no relevant acute inhalation risk, when handling the substance without extensive dust formation. How ever the tes system is unsuitable concerning information going beyond this statement. Acute inhalation toxicity test with dust enriched atmosphere; 8 h whole body exposure; one estimated dose of 0.04 mg/l.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Rats are exposed for 8 h in a dust enriched atmosphere, generated by leading the air though an about 5 cm thick substance layer. Post exposure period is 7 days.

GLP compliance:

no

Test type:

other: acute inhalation hazard test

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

At initiation the age was unknown and mean weight of males was 174 g and of females 156 g
no further data

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

other: air

Details on inhalation exposure:

Dust was generated by bubbling 200 l/h dry air (no CO2) through the solid substance column (volume ca. 50 ml) of about 5 cm above a fritted glass disc in a glass cylinder at a temperature of 20°C.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

8 h

Concentrations:

Estimation of concentration from the amount of TS consumed and the air volume: 0.04 mg/l. No further details.

No. of animals per sex per dose:

6 rats per sex exposed for 8 h. Controls: 3 males and 3 females.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations: daily
- Weighing: at initiation and at termination
- Necropsy performed of survivors and rats found dead
- Other examinations performed: clinical signs

Statistics:

no data

Sex:

male/female

Dose descriptor:

LC0

Effect level:

0.04 mg/L air (nominal)

Exp. duration:

8 h

Remarks on result:

other: dust; estimated concentration

Mortality:

No mortality

Clinical signs:

other: No clinical signs

Body weight:

Normal; compared to controls

Gross pathology:

No effects detected.

Other findings:

No effects in controls exposed to air.

Authors estimation of the exposure concentration presumably via measurement of test substance weight.

Conclusions:

In the inhalation hazard test no effects were detected in male and female rats after exposure to dust for 8 h at 20°C.

Executive summary:

The acute inhalation toxicity test is an unsuitable test system due to the atmosphere generation, the estimation of the exposure concentration, the exposure time and the short post exposure observation period.

Rats were exposed for 8 h to dust generated at 20°C (estimated concentration: 0.04 mg/l). The mortality rate was 0/6 in males and 0/6 in females. No clinical signs were observed during and after exposure. Necropsy after 7 days revealed no treatment related effects.

Conclusion: In the inhalation hazard test no effects were detected in male and female rats after exposure to dust for 8 h at 20°C.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Additional information

ORAL:

The study (BASF AG, 1974) is comparable to OECD Guideline 401 with acceptable restrictions (partly limited documentation, e.g. no details about the test substance; post exposure observation period 7 days). Groups of 5 male and 5 female rats were gavaged with 35 % aqueous HPN (CAS 1115 -20 -4) at dose levels of 4640 and 10000 mg/kg bw with a post exposure observation period of 7 days. Clinical signs occurred immediately after gavage: prone and side position, apathy, atony, gasping, cyanosis, and 2nd day red encrusted noses; symptoms were still present after 2 days. No symptoms were detected 5 days after application. Generally, females were more susceptible than males. The body weight gain was not reduced. Necropsy revealed dilatated heart and some cases of splenomegaly. The oral LD50 is 8000 mg/kg bw in male and female rats combined.

 

INHALATION:

In the available acute inhalation toxicity test (BASF test, 1974) for HPN (CAS 1115 -20 -4) rats were exposed for 8h to HPN dust, generated at 20 °C (estimated concentration 0.05 mg/L). The mortality rate was 0/6 in males and 0/6 in females. No clinical signs were observed during and after exposure. Necropsy after 7 days revealed no treatment related effects. The test demonstrates that there is no relevant acute inhalation risk, when handling the substance without extensive dust formation. However the test system is unsuitable concerning information going beyond this statement.

Justification for classification or non-classification

Due to the results from the acute toxicity studies, classification and labelling according to Annex VI of Directive 67/548/EWG or Annex I of Directive 1272/2008 (EU-GHS) is not required for HPN (= 3-hydroxy-2,2-dimethyl-propyl- 3'-hydroxy-2',2'dimethylpropionate), because - if mortality was observed - it occured above threshold for classification and labeling.